# Renal electrolyte handling in females vs. males over life cycle

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2022 · $604,503

## Abstract

PROJECT SUMMARY
Kidney function is critical to maintaining effective circulating volume (ECV), electrolyte homeostasis and blood
pressure (BP). Dysregulation of fluid and electrolyte transport in the kidney is central to hypertension (HTN)
and cardiovascular disease (CVD) progression. Na+, K+, and volume homeostasis are maintained by regulation
of renal ion and water transporters expressed in tubule specific patterns; K+ balance also depends on
regulation of muscle transporters. HTN and CVD are a function of sex, age and lifestyle; less frequent in
females than males below 65 yr and more common in post-menopausal females vs males over 65 yr; salt
sensitivity of BP increases in both sexes with age. We have reported sex differences in the abundance of
transporters along the nephron in both Sprague Dawley rats (SDR) and C57BL/6J mice, and used
computational models to establish the functional implications of the dimorphisms, e.g. more robust natriuretic
responses in young female vs male SDR. How kidney and muscle transporter profiles respond to life cycle
transitions from development through aging and menopause is not known. Our overarching goal is to
combine experimental and computational approaches to determine how kidney (and muscle) functions
adapt to maintain ECV, electrolyte and fluid homeostasis in response to life cycle challenges in both
male and female rats and mice: from development to aging, through the female-specific challenges of
lactation and menopause, and the common challenges of dietary Na+ and K+. Aim 1. Test the hypothesis
that baseline kidney function adapts during life cycle in a sex-specific manner to maintain fluid and
electrolyte homeostasis. When do transporter sex differences appear? Is the more robust natriuresis in
young females vs males still evident at 12 mo? Do muscle K+ transporters exhibit sex dimorphisms that impact
K+ adaptation with age? We will utilize the Four Core Genotype mouse model to attribute dimorphisms along
life cycle to gonadal hormones vs sex chromosome complement. Aim 2. Describe mechanisms of female
kidney adaptation to lactation. Do kidney and nephron function adapt to maintain maternal homeostasis
during peak lactation at minimal cost? Do kidney function, ECV and electrolyte homeostasis return to baseline
after lactation cessation? Does extrarenal K+ homeostasis (skeletal muscle K+ transporters and [K+]) adapt
during/after lactation? Aim 3. Test the hypothesis that menopause and age reduce sex differences and
increase salt-sensitivity. Does ovotoxin-induced menopause change female kidney and muscle transporter
profiles and function? Is salt-sensitive hypertension sex dependent? Exacerbated after menopause?
Accomplishing these aims will fill important gaps in knowledge about sex-specific mechanisms of Na+, K+, and
volume homeostasis and physiology throughout life cycle, thus, providing a better understanding of the female
advantage in CVD and guiding therapeutic targets in both sexes across life c...

## Key facts

- **NIH application ID:** 10539013
- **Project number:** 2R01DK083785-10A1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** AURELIE EDWARDS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $604,503
- **Award type:** 2
- **Project period:** 2010-08-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10539013

## Citation

> US National Institutes of Health, RePORTER application 10539013, Renal electrolyte handling in females vs. males over life cycle (2R01DK083785-10A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10539013. Licensed CC0.

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